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Ringing the changes - The hard slog of making steroids should soon be a distant memory

点击量:   时间:2018-02-04 07:02:11

By David Bradley A CASCADE of chemical reactions that builds steroids the easy way has been discovered by chemists at the University of Nottingham. The method, which cuts down on labour, waste and solvents, could be a godsend for researchers trying to find better drugs for hormone replacement therapy and oral contraceptives. Steroid molecules are composed of four carbon rings fused together with various chemical groups attached. Animals have the right equipment to make these compounds easily, but for chemists it’s a tougher proposition. The formation of each ring leads to unwanted by-products that have to be separated off before another ring can be added. Gerald Pattenden and his colleagues realised that a type of molecule called a trienone has the right geometry to form four rings in a chain reaction. The molecule they chose has an oxygen atom at one end, plus three reactive carbon-carbon double bonds and a cyclopropane group—a ring of three carbon atoms—strategically placed along a chain of carbon atoms. To kick the reaction off, Pattenden’s team uses a radical initiator—an uncharged molecule with a spare electron. This molecule sends an electron from the carbon next to the oxygen atom towards the cyclopropane, via the double bonds. This forms two rings at the oxygen end. The spare electron, which ends up near the cyclopropane, then unravels this group to form a large third ring. In the final step, a bridge forms across this large ring to leave the four rings characteristic of steroids (Chemical Communications, 1998, p 311). “This is certainly an elegant achievement,” enthuses chemist Dennis Curran of Pittsburgh University in Pennsylvania. “They may be able to make a whole host of steroid isomers, including natural ones.” Pattenden has already made a seven-ring steroid, and is working on an 11-ring version. “If we can start the cascade at one end and then make it double back on itself, we might be able to make sheets of rings,